PROJECT SUMMARY/ABSTRACT Project VI (PVI) of the Florida Learning Disability Research Center (LDRC), titled Imaging genetics in SRD: Mega- and meta-analyses, was designed in response to RFA-HD-17-006's stipulation to obtain converging evidence through the utilization of multiple methodologies?neuroimaging and genetic in the case of PVI?in order to both discover and highlight the most robust and replicable facets of the genome-brain connection in Specific Reading Disabilities (SRD). PVI was contextualized by the overall premise of the P50 to reflect the current status of science in the field of Learning Disabilities (LD) in general and SRD in particular and, therefore, was framed to generate such a reflection in the subfield of imaging genetics of SRD. With that in mind, we proposed a set of imaging-genetic meta-analytic studies. We intend to establish a merged data set that combines behavior, neuroimaging, and genetic (GWAS) data generated by a group of USA and European investigators. Specific Aim 1 (SA1) of PVI is committed to the construction of such a database; it establishes procedures for data merging, quality control, deposition, and manipulation. At the time of the submission of PVI, we had a commitment from contributing investigators to generate a dataset of 1,202 individuals. Since our receiving the funding, we have lost one collaborator (GSU, n=150), but have secured a collaboration with the Healthy Brain Network, HBN (launched by the Child Mind Institute), which can potentially contribute up to 8,649 individuals. In this Supplement, we are proposing to incorporate a subsample of 2,000 individuals from the HBN into our dataset. SA2 is a continuation and extension of the activities of PVI established over the two previous cycles of funding. This aim will provide an opportunity to interrogate the genetic findings assembled in PVI so far for their robustness, replicability, and generalizability using these merged data. Thus, SA2 assures the continuity of the PVI work carried out in the two generations of the Florida LDRC. In contrast, SA3 is exploratory and innovative, both to the field of SRD and to PVI. It proposes a reversed GWAS that capitalizes on the availability of multiple neuroimaging phenotypes in the large merged dataset that we will assemble in SA1. To maintain the spirit and the scope of the proposed work, we will utilize behavioral data only for the purpose of grouping or controlling for level of performance in SA2 and SA3. The current iteration of PVI corresponds to the general theme of the third-generation Florida LDRC: it capitalizes on its own trajectory developed throughout the two previous cycles of funding; proposes a set of mega- and meta-analytic studies; and creates an opportunity to utilize and further develop a curated communal resource that has the potential to become a platform for reproducibility tests in the field of SRD. The proposed Supplement allows the utilization of the HBN sample, in which comparable behavior and brain phenotypes are available, however, DNA samples need to be genotyped. The addition of these data will triple our sample size and create, to our knowledge, an unprecedented database that has not been previously available in the field of SRD.